CoREST: A functional corepressor required for regulation of neural-specific gene expression

Several genes encoding proteins critical to the neuronal phenotype, such as the brain type II sodium channel gene, are expressed to high levels only i n neurons. This cell specificity is due, in part, to long-term repression i n nonneural cells mediated by the repressor protein REST/NRSF (RE1 silencin g transcription factor/neutral-restrictive silencing factor). We show here that CoREST, a newly identified human protein, functions as a corepressor f or REST. A single zinc finger motif in REST is required for CoREST interact ion. Mutations of the motif that disrupt binding also abrogate repression. When fused to a Ga14 DNA-binding domain, CoREST functions as a repressor, C oREST is present in cell lines that express REST, and the proteins are foun d in the same immunocomplex. CoREST contains two SANT (SW13/ADA2/NCoR/TFIII B B) domains, a structural feature of the nuclear receptor and silencing me diator for retinoid and thyroid human receptors (SMRT)-extended corepressor s that mediate inducible repression by steroid hormone receptors, Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repre ssion essential to maintenance of cell identity.